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Evolution Basics: At the Frontiers of Evolution, Part 3: The RNA World Hypothesis

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August 7, 2014 Tags: Genetics, History of Life

Today's entry was written by Dennis Venema. You can read more about what we believe here.

Evolution Basics: At the Frontiers of Evolution, Part 3: The RNA World Hypothesis

Note: This series of posts is intended as a basic introduction to the science of evolution for non-specialists. You can see the introduction to this series here. In this post we explore the “RNA world” – a proposed stage in the origin of life that predates modern DNA and protein-based biochemistry.

Weizsäcker’s book The World View of Physics is still keeping me very busy. It has again brought home to me quite clearly how wrong it is to use God as a stop-gap for the incompleteness of our knowledge. If in fact the frontiers of knowledge are being pushed back (and that is bound to be the case), then God is being pushed back with them, and is therefore continually in retreat. We are to find God in what we know, not in what we don’t know; God wants us to realize his presence, not in unsolved problems but in those that are solved.

Dietrich Bonhoeffer, Letters and Papers from Prison

In the last post in this series, we introduced the “RNA world” hypothesis – the idea that life was RNA based prior to DNA-based biochemistry. As we noted, this hypothesis received a great boost in the early 2000s, when it was determined that the ribosome – the enzyme responsible for making proteins from information coded in DNA and RNA – was in fact a ribozyme: an enzyme constructed out of RNA.

We can better appreciate ribozymes for the marvels that they are with a brief review of some basic cell biology we covered earlier in the series (and those requiring a more thorough refresher can use the links provided). You might recall that DNA is a polymer formed from monomers, and that the information in DNA is transferred to proteins, which have a three-dimensional shape that can perform structural and enzymatic functions. In this way, DNA functions as a hereditary molecule and proteins do the day-to-day work in the cell. “Messenger RNA”, as we discussed, is the intermediate between DNA and protein. As a “working copy” of a gene, messenger RNA is used as a template for directing the order of monomers in the resulting protein. What we did not discuss, however, is the key role that a different type of RNA plays in this process – the RNA that makes up the enzymatic core of the ribosome, the enzyme that connects protein monomers together as directed by the messenger RNA.

Full length hammerhead ribozyme
Image credit: William G. Scott. [CC BY-SA 3.0].

These RNA molecules, called “rRNA” for “ribosomal RNA” are strings of monomers similar to DNA monomers. Yet these molecules also have an enzymatic function that depends on their three-dimensional shape – their sequences direct them to fold up into a structure that can perform an enzymatic function. In this way, they are similar to proteins, which also fold up into functional shapes to do their jobs. Despite this shape, they remain a polymer that in principle can be used as a template for replicating themselves, much like DNA. While it is not possible to show a complete structure of rRNA here (since it is such a large molecule), a smaller ribozyme can be used to illustrate its features: a string of nucleotide monomers that folds up to form an active enzyme based on its three-dimensional shape:

Given that RNA can have both DNA-like and protein-like attributes, it’s not surprising that researchers have proposed that RNA in fact precedes both. From the beginning of this hypothesis, one of the key goals of researchers investigating the RNA world has been to identify a self-replicating RNA ribozyme. Such a molecule would have the essential ingredients for evolution: a genome subject to mutation, thereby producing genetically different “offspring” that would be subject to natural selection.

Challenges and difficulties

One of the main problems with the RNA world hypothesis, among many (after all, this is a frontier area), is that as far as we can tell, a self-replicating RNA ribozyme needs to be quite complex. To date, scientists have not succeeded in identifying an RNA sequence that is capable of being a general RNA replicator, and RNA molecules that do have at least some ability to replicate RNA tend to be quite long (i.e. comprised of many building blocks). The probability that such a molecule would arise spontaneously from a pre-biotic mixture of chemicals is vanishingly slim, even if one grants an environment where the required chemicals are common (a problem in itself that we will discuss further below).

One conjecture that addresses this issue is the idea that the original self-replicating RNA ribozyme was not a single molecule, but rather a collection of molecules – a sort of molecular ecosystem where a number of smaller RNA molecules contribute to the replication of the entire set. Such a system might be easier to hit upon by chance (since each individual molecule is less complex), or, conversely, such a system might be easier to develop from some as-yet-unknown precursor system.

While seemingly farfetched, this idea recently received some empirical support. In this paper, a research group reports their findings that self-sustaining catalytic networks of small RNA molecules can spontaneously arise from mixed populations of RNA precursors, and that such networks can evolve increased complexity over time. While far from solving all of the problems with the RNA world hypothesis, these results indicate that the first RNA-dependent RNA replicating enzyme was in fact a population of small, simpler RNA molecules rather than one large and complex one.

Further challenges and difficulties

Despite these recent advances, one of the longstanding challenges to the RNA world hypothesis remains: the difficulty of the required precursors arising directly through pre-biotic chemistry. RNA ribozymes, while simpler than cellular life, are themselves quite complex, and formed from relatively complex precursors. While the evidence we have is suggestive that life went through an RNA world stage, recent work has not demonstrated an easy path by which such a world could form directly from nonliving components. Accordingly, some researchers have begun to search for other “worlds” – simpler ones that predate the RNA world, and might have served as an intermediate stepping-stone on the gradient between non-living chemistry and RNA-based life. While this work is by its nature quite speculative (it is, after all, the frontier of a frontier) recent work has supported the hypothesis that RNA could have been preceded by simpler chemistry more amenable to spontaneous assembly in a pre-biotic chemical mixture. In the coming years it will be interesting to see if any of these hypotheses gain additional support. After all, for a research scientist, the frontiers are the exciting areas – and few areas in evolution are more at the frontier than work on abiogenesis.

So, will science ever solve the problem of abiogenesis? Perhaps not – though when I reflect on the fact that we are only 400 years removed from the time of Galileo, I am reminded that many seemingly unsolvable scientific problems have indeed been solved. And along with Bonhoeffer, I delight in these scientific advances that give us an ever-larger picture of God and his faithfulness to his creation.

In the next post in this series, we’ll move on to another frontier area of evolutionary biology – the ongoing debate between those who view evolution as a primarily convergent process, and those who see evolution as primarily driven by chance events (i.e. as a contingent process).

For further reading


Dennis Venema is professor of biology at Trinity Western University in Langley, British Columbia. He holds a B.Sc. (with Honors) from the University of British Columbia (1996), and received his Ph.D. from the University of British Columbia in 2003. His research is focused on the genetics of pattern formation and signaling using the common fruit fly Drosophila melanogaster as a model organism. Dennis is a gifted thinker and writer on matters of science and faith, but also an award-winning biology teacher—he won the 2008 College Biology Teaching Award from the National Association of Biology Teachers. He and his family enjoy numerous outdoor activities that the Canadian Pacific coast region has to offer. Dennis writes regularly for the BioLogos Forum about the biological evidence for evolution.

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sy - #86154

August 7th 2014

Dennis

My problem with RNA world is not what came before, but what came after. I dont see how ribozymes can evolve (they dont do so naturally), and I cant see how RNA world can turn into DNA world with a genetic code. One issue is that if RNA world were real, there would have had to have been many ribozymes in a proto cell. How could they all evolve together? Evolution as we know it requires an error free translation system. Ribozymes cant accomplish that. 

Another point is that there is actually no evidence at all for RNA world. What there is is some speculation that such life might have existed, and some (very weak) evidence that it could have existed. 


melanogaster - #86392

August 27th 2014

Sy wrote:

“My problem with RNA world is not what came before, but what came after. I dont see how ribozymes can evolve (they dont do so naturally),...”

How do you know this? Are you claiming that the ribosome and other ribozymes have not evolved?

“...and I cant see how RNA world can turn into DNA world with a genetic code.”

So because you can’t see something, that’s it? Haven’t you witnessed the identification of many pathways in biology that you didn’t see coming?

“One issue is that if RNA world were real, there would have had to have been many ribozymes in a proto cell. How could they all evolve together?”

By variation and selection.

“Evolution as we know it requires an error free translation system.”

Hmmm…is translation error free?

“Another point is that there is actually no evidence at all for RNA world.”

The arrogance of this statement is staggering. How is the fact that the ribosome is a ribozyme not extremely strong evidence of an RNA World? In your mind, what is it evidence for? How do you explain it?


g kc - #86157

August 7th 2014

Dennis,

I have three points I hope you will address.

1)

“As we noted, this hypothesis received a great boost in the early 2000s, when it was determined that the ribosome – the enzyme responsible for making proteins from information coded in DNA and RNA – was in fact a ribozyme: an enzyme constructed out of RNA.”

This sounds as though the ribozyme makes proteins from RNA but at the same time is made up of RNA. This seems circular, like a chicken or egg puzzle. Am I not understanding this correctly?

 

2)

“One conjecture that addresses this issue is the idea that the original self-replicating RNA ribozyme was not a single molecule, but rather a collection of molecules – a sort of molecular ecosystem where a number of smaller RNA molecules contribute to the replication of the entire set. Such a system might be easier to hit upon by chance (since each individual molecule is less complex), or, conversely, such a system might be easier to develop from some as-yet-unknown precursor system.”

This conjecture appears to be seeking a way around the great complexity of the hypothesized first RNA molecule (“… small, simpler RNA molecules rather than one large and complex one”). However, this requires a system, a mechanism of multiple parts working together for a common goal. The proposed smaller RNA molecules may be simpler, but they require successful integration with other small RNA molecules in an effective system. One complexity (the large complex RNA molecule) exchanged for perhaps greater complexity (small RNA molecules in a complex system). Some might say the latter is less complex than the former. I’m not convinced. Here’s an analogy: Which would be more difficult, more complex to achieve, between

- Having one extraordinary, genius scientist who individually solves a great problem, or

- Getting many ordinary, “normal” scientists to work together in a committee of sorts to solve the same great problem?

I think the latter is more difficult to pull off. Others who have experience with group projects and committees might agree.

3)

“… few areas in evolution are more at the frontier than work on abiogenesis.”

I have read many times that evolution does not address abiogenesis or the origin of life, that evolution explains only what happened after the first life came to be. Is abiogenesis and origin of life now part of evolution theory?


g kc - #86163

August 9th 2014

Dennis,

I have a fourth question on this subject.

This article makes multiple mentions of DNA, RNA, and ribozymes, and I’m confident everyone agrees that these things exist. But you also repeatedly note “self-replicating” in regard to the ribozyme. I was most surprised by this sentence:

“While far from solving all of the problems with the RNA world hypothesis, these results indicate that the first RNA-dependent RNA replicating enzyme was in fact a population of small, simpler RNA molecules rather than one large and complex one.”

I’ve read a bit on this subject, including some of the work by Nobel Prize winner Jack Szostak of Harvard Medical School. I don’t recall reading of any discoveries, or even artificial manufacturing, of self-replicating ribozymes. Yet the quote above clearly appears, to me, to be a putative statement – that such self-replication does, or at least did, exist.

My question is: Forgetting about the first one, has anyone ever discovered any self-replicating ribozyme?


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